Age and Infectious Dose Significantly Affect Disease Progression after RHDV2 Infection in Naïve Domestic Rabbits.

Robyn N Hall,Melissa Piper,Tegan King,Jane Arrow,Tiffany O'Connor,Andrew J Read,Tanja Strive,Janine Duckworth,Katherine Trought

doi:10.3390/v13061184

Abstract

Rabbit haemorrhagic disease virus 2 (RHDV2 or GI.2, referring to any virus with lagovirus GI.2 structural genes) is a recently emerged calicivirus that causes generalised hepatic necrosis and disseminated intravascular coagulation leading to death in susceptible lagomorphs (rabbits and hares). Previous studies investigating the virulence of RHDV2 have reported conflicting results, with case fatality rates ranging from 0% to 100% even within a single study. Lagoviruses are of particular importance in Australia and New Zealand where they are used as biocontrol agents to manage wild rabbit populations, which threaten over 300 native species and result in economic impacts in excess of $200 million AUD annually to Australian agricultural industries. It is critically important that any pest control method is both highly effective (i.e., virulent, in the context of viral biocontrols) and has minimal animal welfare impacts. To determine whether RHDV2 might be a suitable candidate biocontrol agent, we investigated the virulence and disease progression of a naturally occurring Australian recombinant RHDV2 in both 5-week-old and 11-week-old New Zealand White laboratory rabbits after either high or low dose oral infection. Objective measures of disease progression were recorded through continuous body temperature monitoring collars, continuous activity monitors, and twice daily observations. We observed a 100% case fatality rate in both infected kittens and adult rabbits after either high dose or low dose infection. Clinical signs of disease, such as pyrexia, weight loss, and reduced activity, were evident in the late stages of infection. Clinical disease, i.e., welfare impacts, were limited to the period after the onset of pyrexia, lasting on average 12 h and increasing in severity as disease progressed. These findings confirm the high virulence of this RHDV2 variant in naïve rabbits. While age and infectious dose significantly affected disease progression, the case fatality rate was consistently 100% under all conditions tested.

Highlights

Rabbit haemorrhagic disease is a peracute, typically fatal, hepatitis of European rabbits (Oryctolagus cuniculus) culminating in generalised hepatic necrosis and disseminated intravascular coagulation in susceptible individuals [1]
We observed a 100% case fatality rates (CFR) in all infected rabbits regardless of age or infectious dose, while all the control animals survived until the end of the experiment (10 dpi) (Figure 2A)
In the adult rabbit groups, survival time was significantly shorter in rabbits infected with a high virus dose than in those infected with a low virus dose (Figure 2A,B, Supplementary Table S2)

Summary

Introduction

Rabbit haemorrhagic disease is a peracute, typically fatal, hepatitis of European rabbits (Oryctolagus cuniculus) culminating in generalised hepatic necrosis and disseminated intravascular coagulation in susceptible individuals [1]. In Australia and New Zealand, it was deliberately released as a viral biocontrol agent to manage wild rabbit populations It arrived in other regions through natural and/or anthropogenic transmission routes, and caused sporadic disease in Mexico, USA, Uruguay, Canada, and elsewhere [1]. RHDV2 rapidly spread via natural transmission pathways throughout Europe, parts of Africa and the Middle East, Australia, and Canada, and has recently been reported in wild Lepus and Sylvilagus species in the USA [10,11]. It is the dominant pathogenic lagovirus in these geographic regions

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